Individual differences in drug abuse vulnerabilities among humans are likely to display genetic as well as environmental components. During this year, these investigators continued to explore possible roles of allelic variants at candidate gene loci in possibly contributing to human individual differences in drug abuse vulnerability. We published updated reports of convergence of the several genome scanning approaches to identifying previously-unanticipated gene loci conferring drug abuse vulnerabilities. We continued to make major advances in providing simulations and modeling for the power of genome-wide and focused association/linkage-disequilibrium based genome scanning. Work during this year provided replication and extension of identificaiton of candidate regions on several human chromosomes using high-density SNP and SSLP-based linkage-disequilibrium based genome scanning, generating more than 55 million person/genotypes. Data is consistent with the emerging models that genetic influences are polygenic, with few major gene influences. Several chromosomal regions previously nomninated by our studies have been replicated in new work completed during this year. Fine mapping studies have identified particular haplotypes at several gene loci that represent the strongest candidates for addiction vulnerability genes in humans. During this year, we also reported the first estimates for the impact of complex genetics on US vulnerability to brain disorders, highlighting the large contributions that these polygenic determinants are likely to exert on addiction.